86 articles - From Friday Nov 18 2022 to Friday Nov 25 2022
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer: a pooled analysis. Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC. |
Molecular and clinical diversity in primary central nervous system lymphoma. The integration of genome-wide data from multi-omics data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions. |
Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: A prospective multi-center randomized clinical trial. NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC. |
| Blood |
A phase 2 study of Interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This work was supported by funding from Evive Biotech., The Society of Memorial Sloan Kettering Cancer Center, and the National Institutes of Health. |
Allogeneic natural killer cell therapy. Basic advances in NK cells biology and cellular engineering have led to new translational strategies to block inhibition, enhance and broaden target cell recognition, optimize functional persistence, and provide stealth from patients' immunity. This review details NK cell biology, as well as NK cell product manufacturing, engineering, and combination therapies explored in the clinic leading to the next generation of potent, off-the-shelf cellular therapies for blood cancers. |
Determining venous thromboembolism risk in patients with adult-type diffuse glioma. These ten variables were used to create a web-based VTE prediction tool which was validated in two separate cohorts of adult-type diffuse glioma patients from other institutions. This study extends our understanding of the VTE landscape in these tumors, and provides evidence-based guidance for clinicians to mitigate VTE risk in glioma patients. |
FLT3ITD drives context-specific changes in cell identity and variable interferon dependence during AML initiation. Thus, common AML driver mutations, such as FLT3ITD, can co-opt different mechanisms of transformation in different genetic contexts. Furthermore, pediatric-biased NUP98 fusions convey actionable interferon dependence. |
How I treat Elderly Patients with DLBCL in the frontline setting. Further progress can be expected from non-chemotherapy based therapies, such as bispecific antibodies, antibody-drug conjugates and immunomodulatory agents. This article provides an overview of first line treatment in elderly patients with DLBCL and our approach to the management of these challenging patients. |
How we diagnose and treat acute graft-versus-host disease after solid organ transplantation. For GVHD involving the marrow we initiate an allogeneic hematopoietic cell donor search early. In this article, we describe three cases of GVHD after SOT, outline our approach to diagnosis and management, and then provide analysis of the three instructive cases. |
How We Use Risk Factors for Success or Failure of CD19 CAR T-cells to Guide Management of Children/AYA with B-cell ALL. We include data from both prospective and recent large retrospective studies that offer insight into understanding when risks of CAR T-cell therapy failure are high and offer perspectives suggesting when consolidative hematopoietic cell transplantation (HCT) or experimental CAR T-cell and/or alternative immunotherapy should be considered. We also propose areas where prospective trials addressing optimal use of CAR T-cell therapy are needed. |
Kruppel-like factor 1-GATA1 fusion protein improves the sickle cell disease phenotype in mice both in vitro and in vivo. Transplantation of highly purified SCD mouse HSCs expressing KLF1-GATA1 fusion protein into SCD mice lessened the severity of the anemia, reduced the sickling of red blood cells, improved SCD-related pathological alterations in spleen, kidney, and liver, and restored urine-concentrating ability in recipient mice. Taken together, these results indicate that the use of KLF1-GATA1 fusion constructs may represent a new gene therapy approach for hemoglobinopathies. |
North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: Position on Standards of Care and Areas of Need. This group of experts includes a multi-disciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, and was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein. |
Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis. Altered distribution of filamin A and actin and delocalization of the von Willebrand Factor were also demonstrated. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasized the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function. |
| Blood Adv |
Anti-HK antibody inhibits the plasma contact system by blocking prekallikrein and factor XI activation in vivo. Moreover, 3E8 blocked PKa binding to HK and dose-dependently inhibited PKa cleavage of HK. Our results reveal a novel strategy to inhibit contact system activation in vivo, which may provide an effective method to treat human diseases involving contact system dysregulation. |
Anti-leukemic properties of the kinase inhibitor OTSSP167 in T cell acute lymphoblastic leukemia. OTSSP167 exhibited synergistic interactions when combined with dexamethasone, L-asparaginase, vincristine, and etoposide. Our findings reveal novel anti-leukemic properties of OTSSP167 in T-ALL and support the use of OTSSP167 as an adjuvant drug to increase treatment response and reduce relapses in pediatric T-ALL. |
Coping in Caregivers of Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation. Our findings suggest that coping is related to distress and QOL among caregivers of HSCT recipients even pre-transplant. Hence, caregivers of patients with hematologic malignancies undergoing HSCT may benefit from resources that facilitate adaptive coping with the demands of caregiving. |
Dynamin-2 deficiency causes age- and sex-dependent neutropenia and myelodysplasia in mice. In summary, female mice with bone marrow Dnm2 haploinsufficiency developed neutropenia as they aged with decreased granulocyte progenitor production and migration defects. Our studies indicate a potential mechanism for the development of chronic idiopathic neutropenia, a disease that predominantly presents in middle-aged women. |
Efficacy, Safety, and Molecular Response Predictors of Oral Ixazomib and Short-Course Rituximab in Untreated iNHL. Ixazomib demonstrated efficacy alone and with short course rituximab in untreated iNHL while exhibiting favorable toxicity, convenience, and retention of B-cell immune response. This trial is registered at as NCT02339922. |
Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pre-treatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients prior to anti-CD19 CAR T-cell therapy. |
Levofloxacin prophylaxis vs no prophylaxis in neutropenic patients within an endemic country for carbapenem-resistant GNB. Comparing antimicrobial resistance among Gram-negative bacteria in the setting of allo-HSCT, in the group without FQ-P a significantly higher proportion of pathogens was susceptible to piperacillin/tazobactam (71% versus 30%, p=0.026), FQ (49% versus 10%, p=0.03) and carbapenems (95% versus 50%, p=0.001). FQ-P discontinuation increased Gram-negative bacteria PE-BSI, but it did not impact IRM, both in ASCT and allo-HSCT setting; importantly, it concurred to decrease significantly antimicrobial resistance in Gram-negative bacteria. |
Open-Label, Pilot Study of Romiplostim for Thrombocytopenia After Autologous Hematopoietic Cell Transplantation. Only 1 adverse event was deemed possibly attributable to romiplostim, a low-risk pulmonary embolism in a patient with multiple myeloma. In conclusion, romiplostim showed promising activity and safety after autoHCT, but the improvement in platelet counts occurred later than the goal of shortening the duration and depth of the platelet nadir. |
Optical Genome Mapping in Acute Myeloid Leukemia: A Multicenter Evaluation. The results from this multi-institutional study indicate that OGM effectively recovers clinically relevant SVs and CNVs found by standard of care methods and reveals additional SVs not reported. Furthermore, OGM minimizes the need for labor-intensive multiple cytogenetic tests while concomitantly maximizing diagnostic detection through a standardized workflow. |
Peripheral Blood Monocyte Count is a Dynamic Prognostic Biomarker in Multiple Myeloma. Abnormal AMC was also associated with inferior OS independent of validated prognostic markers including the international staging system stage ISS Stage, and high lactate dehydrogenase LDH. Our findings provide novel clues for future prospective studies on the functional role of monocytes in multiple myeloma, which could be a readily available metric for risk stratification. |
The complement receptor C3AR constitutes a novel therapeutic target in NPM1-mutated AML. Mechanistically, stimulation of C3AR-expressing cells with C3a, the ligand of C3AR, leads to activation of ERK1/2 and increased survival of AML cells, suggesting that this is an important signaling axis in this subtype of AML. Finally, we show that antibodies directed against C3AR efficiently elicit NK cell-mediated killing of primary AML cells ex vivo, highlighting C3AR as a candidate therapeutic target in NPM1-mutated AML. |
Transcriptional reprogramming of infiltrating neutrophils drives lung disease in severe COVID-19 despite low viral load. In addition, exacerbated neutrophil production of IL-8, IL-1ß, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of a transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to ARDS in a well-defined patient population disproportionally affected by severe COVID-19. |
Underweight children over 5 years with sickle cell anemia are at risk for early mortality in a low-resource setting. Underweight participants (weight-for-age z-score < -1) had a greater probability of death during follow-up than those not underweight (p=0.043). Underweight status in school-aged children with sickle cell anemia is a previously unrecognized risk factor for early mortality in Nigeria and can be easily applied to screen children at risk for death. |
| Blood Cancer J |
An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P |
Validation of the revised diagnostic criteria for primary plasma cell leukemia by the Korean Multiple Myeloma Working Party. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum ß2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs = 5% in a peripheral blood smear is appropriate for PCL diagnosis. |
| Haematologica |
Animal models of Diamond-Blackfan anemia: updates and challenges. In the past decades, researchers have made significant progress in understanding the pathogenesis of DBA, but it remains unclear how the ubiquitous RP haploinsufficiency causes the erythroid-specific defect in hematopoiesis in DBA patients, and why there is a difference in penetrance and spontaneous remission among individuals who carry identical mutations. In this paper, we provide a comprehensive review of the development of DBA animal models and discuss the future research directions for these important experimental systems. |
Diffuse large B-cell lymphoma in octogenarians aged 85 and older can benefit from treatment with curative intent: a report on 129 patients prospectively registered in the Elderly Project of the Fondazione Italiana Linfomi (FIL). Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs 23%: P=0.001) and had worse 2-year overall survival (OS) (48% vs 63%: P=0.001) and 2-year progression-free survival (PFS) (43% vs 56%: P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P. |
Hyperactive CREB subpopulations increase during therapy in paediatric B lineage acute lymphoblastic leukaemia. The small molecule CREB inhibitor, 666-15, was shown to reduce CREB transcriptional activity and induce apoptosis in ALL PDX cells of varying cytogenetic subtypes in vitro, both in the presence and absence of stromal support. Together, these data suggest that the cAMP signalling pathway may provide an opportunity for MRD-directed therapy for many patients at high risk of relapse. |
Prevention and management of secondary central nervous system lymphoma. In this review we focus on the identification of high-risk patients, prophylaxis strategies and recent treatment approaches for SCNSL. The incorporation of novel agents to immunochemotherapy deserves further study in prospective trials. |
Targeting glutaminase is therapeutically effective in ibrutinib-resistant mantle cell lymphoma. Moreover, telaglenastat showed anti-MCL synergy when combined with ibrutinib or venetoclax in vitro, which was confirmed using an MCL patient-derived xenograft model. Our study provides the first evidence that targeting GLS with telaglenastat, alone or in combination with ibrutinib or venetoclax, is a promising strategy to overcome ibrutinib resistance in MCL. |
| Lancet Haematol |
Brentuximab vedotin plus nivolumab after autologous haematopoietic stem-cell transplantation for adult patients with high-risk classic Hodgkin lymphoma: a multicentre, phase 2 trial. Combination immunotherapy in this setting should be further studied in patients with classic Hodgkin lymphoma with further refinement of the regimen to mitigate toxic effects, particularly in high-risk patients in whom more intensive therapy to prevent relapse is warranted. Funding Bristol Myers Squibb, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and National Cancer Institute of the National Institutes of Health. |
Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Patients with newly diagnosed Ph-positive acute lymphoblastic leukaemia could be spared the toxicities associated with chemotherapy and the need for allogeneic haematopoietic stem-cell transplantation in first response. Funding Takeda Oncology and Amgen. |
Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib. Funding BeiGene. |
| Leukemia |
Isocitrate dehydrogenase 1 mutation drives leukemogenesis by PDGFRA activation due to insulator disruption in acute myeloid leukemia (AML). R132H mutation leads to CTCF hypermethylation, disrupting DNA-looping and insulation of PDGFRA, resulting in PDGFRA upregulation in IDH1-mutant AML. Treatment with dasatinib may offer a novel treatment strategy for IDH1-mutant AML. |
P2X1 enhances leukemogenesis through PBX3-BCAT1 pathways. The P2X1 antagonist sufficiently suppressed AML cell proliferation. These results provided a unique perspective on how metabolic niche factor ATP fine-tunes LIC activities, which may benefit the development of strategies for targeting LICs or other cancer stem cells. |
Targeting cell cycle and apoptosis to overcome chemotherapy resistance in acute myeloid leukemia. Additionally, direct promotion of apoptosis with venetoclax, showed substantial synergy with chemotherapy, overcoming resistance mediated by impaired cell cycle arrest. Altogether, we identify defective cell cycle arrest as a clinically relevant contributor to chemoresistance and identify rationally designed therapeutic combinations that enhance response in AML, potentially circumventing chemoresistance. |
| Thromb Haemost |
Assessment of DOAC in GEriatrics (ADAGE study): rivaroxaban/apixaban concentrations and thrombin generation profiles in NVAF very elderly patients. Our study provides original data in very elderly patients receiving DOAC in real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings. |
Association between sports participation, factor VIII levels and bleeding in hemophilia A. This analysis showed that FVIII levels were an important determinant of the bleeding hazard, but sports participation was not. This observation most likely reflects the presence of adequate FVIII levels during sports participation in our study. Persons with severe hemophilia A exhibited a higher bleeding hazard at a similar FVIII levels than non-severe, suggesting that the time spent at lower FVIII levels impacts overall bleeding hazard. These data may be used to counsel persons with hemophilia regarding sports participation and the necessity of adequate prophylaxis. |
Genetic predisposition of both waist circumference and hip circumference increased the risk of venous thromboembolism. There is a significant causal relationship between WC/HC and VTE/PE, which is consistent with observational studies. Taking measures to reduce WC/HC of obesity may help reduce the incidence of VTE/PE. |
Obesity and the Risk of Venous Thromboembolism after Major Lower Limb Orthopaedic Surgery: A Literature Review. Hence any increase in dosage may require intensive surveillance for the residual anticoagulant effects and careful balancing of risks and benefits on an individual basis. Our review discusses the basis for increased thrombotic risk in obesity, the evidence supporting dosage recommendations, and the implications of the current guidelines for pharmacological thromboprophylaxis in patients with obesity undergoing lower limb arthroplasty. |
Severe left atrial spontaneous echo contrast in non-valvular atrial fibrillation: Clinical characteristics and impact on ischemic risk post-ablation. Higher BNP, ESR, LAd/ |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Bruton tyrosine kinase inhibitors in the management of Waldenström macroglobulinemia. Although associated with high rates of durable responses, unmet needs with BTK inhibitor therapy include indefinite duration therapy, high cost, scarcity of complete responses, and lower rates and shorter duration of response in patients with CXCR4 mutations. Herein, we review the data supporting the use of covalent BTK inhibitors, selected management issues, clinical trials with covalent BTK inhibitor combination regimens, and up-and-coming non-covalent BTK inhibitors. |
| Blood |
| Leukemia |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
| J Hematol Oncol |
SIRPa-Fc fusion protein IMM01 exhibits dual anti-tumor activities by targeting CD47/SIRPa signal pathway via blocking the "don't eat me" signal and activating the "eat me" signal. Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines. |
| Leukemia |